This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These experiments will provide important preliminary data for the development of the SIV foreskin/penile macaque challenge model. Based on the finding from the Merck STEP trial, in which vaccinated men with a foreskin were more likely to become HIV+, we propose that the foreskin challenge route should be utilized as a mucosal challenge route in future SIV vaccines. Optimizing the foreskin/penile challenge route will be important to test vaccines via this important mucosal route in the SIV/monkey model. Thus far our one attempt at initiating an infection in the four macaques has not been successful. Future experiments will utilize a coinfection model to evaluate the factors that influence SIV infection via the foreskin.